De Nicola L, Blantz R C, Gabbai F B
Division of Nephrology-Hypertension, University of California, San Diego School of Medicine.
Diabetes. 1992 Mar;41(3):267-73. doi: 10.2337/diab.41.3.267.
The role of renal functional reserve (RFR; increase in plasma flow and glomerular filtration rate in response to protein loading) as an indicator of increased glomerular hydrostatic pressure and flow was evaluated in recent-onset poorly controlled diabetic rats. Streptozocin-induced diabetic (STZ-D) rats were studied with micropuncture (MP) technique after 10-15 days of diabetes (daily blood glucose level 15.3-18 mmol). We also studied STZ-D rats treated with the converting-enzyme inhibitor (CEI) enalapril or the angiotensin II (ANG II) receptor antagonist DuP 753 (DuP) for 3 days before MP. Nondiabetic rats (NOR) served as controls. Glomerular hemodynamics and proximal tubular reabsorption were measured in the control period and during intravenous glycine infusion. In NOR rats, glycine increased single-nephron plasma flow (SNPF) and single-nephron glomerular filtration rate (SNGFR). Although STZ-D rats did not exhibit hyperfiltration, SNGFR and SNPF were not modified by glycine, defining loss of RFR. CEI rats responded to glycine with an increase in SNGFR due to a rise in SNPF and a rise in the ultrafiltration coefficient. Interestingly, loss of RFR in STZ-D rats was associated with a decrease in absolute proximal reabsorption. The decrease in absolute proximal reabsorption was corrected by both CEI and DuP, although glomerular vasodilation was restored only in the CEI group. In conclusion, at the early stage of diabetes mellitus, loss of RFR does not detect hyperfiltration, but rather the presence of a tubular alteration probably dependent on ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)
在新近发病且血糖控制不佳的糖尿病大鼠中，评估了肾功储备（RFR；蛋白质负荷后血浆流量和肾小球滤过率的增加）作为肾小球静水压和血流量增加指标的作用。采用链脲佐菌素诱导的糖尿病（STZ-D）大鼠，在糖尿病发病10 - 15天（每日血糖水平15.3 - 18 mmol）后，运用微穿刺（MP）技术进行研究。我们还研究了在MP前3天用转化酶抑制剂（CEI）依那普利或血管紧张素II（ANG II）受体拮抗剂DuP 753（DuP）治疗的STZ-D大鼠。非糖尿病大鼠（NOR）作为对照。在对照期和静脉输注甘氨酸期间测量肾小球血流动力学和近端肾小管重吸收。在NOR大鼠中，甘氨酸增加了单肾单位血浆流量（SNPF）和单肾单位肾小球滤过率（SNGFR）。虽然STZ-D大鼠未表现出超滤，但SNGFR和SNPF未被甘氨酸改变，这表明RFR丧失。CEI大鼠对甘氨酸的反应是SNGFR增加，这是由于SNPF增加和超滤系数升高。有趣的是，STZ-D大鼠中RFR的丧失与绝对近端重吸收的减少有关。CEI和DuP都纠正了绝对近端重吸收的减少，尽管仅在CEI组中恢复了肾小球血管舒张。总之，在糖尿病早期，RFR丧失并未检测到超滤，而是检测到可能依赖于ANG II的肾小管改变。（摘要截短于250字）
